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Comparison of the effect of isosorbide mononitrate combined with misoprostol and misoprostol alone in labor induction in postterm pregnancies: a systematic review and meta-analysis

Document Type : Review Article

Authors
Elham Manouchehri 1
Somayeh Makvandi 2
Leila Karimi 3
Zahra Hadizadeh Talasaz 4
Mona Larki 5
1 Assistant Professor, Department of Nursing and Midwifery, MMS.C, Islamic Azad University, Mashhad, Iran
2 Assistant Professor, Department of Midwifery, Menopause Andropause Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Assistant Professor, Behavioral Sciences Research Center, Life Style Institute, Faculty of Nursing, Baqiyatallah University of Medical Sciences, Tehran, Iran
4 Nursing and Midwifery Care Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Assistant Professor, Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran
5 , Nursing and Midwifery Care Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Assistant Professor, Department of Midwifery, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/nnj.2026.97136.1562
Abstract
Background and Aims: Background: Post-term pregnancy is one of the most frequent indicators of labor induction. For post-term management, clinical settings use misoprostol and nitric oxide donors, such as isosorbide mononitrate (ISMN). But evidence from trials is controversial. This study aimed to synthesize the clinical outcomes of post-term pregnancy management with ISMN and misoprostol combined versus misoprostol alone.
Materials and Methods: The search strategy was carried out for PubMed, Scopus, Web-of-Science, Science Direct, Cochrane Library, Google Scholar, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform until June 20, 2024. We used the second risk-of-bias (RoB2) instrument to assess the bias of randomized clinical trials (RCTs). Meta-analysis data were performed on RevMan 5.4.
Results: The systematic review included six RCTs and five meta-analyses, ranging in quality from low to high. ISMN plus misoprostol significantly reduced the interval from the intervention to the delivery by 4.07 hours (95% CI -5.21 to -2.93, P<0.0001). The ISMN plus misoprostol group had a 0.72-hour shorter interval from the intervention to the beginning of the active labor than the control group, but this difference was not statistically significant (MD = -0.72, CI -2.96 to 1.52, P = 0.53). The risk of vaginal delivery was not statistically different between the control and ISMN plus misoprostol groups (RR = 1.07, CI 0.93 to 1.22, P = 0.37).
Conclusions: The combination of ISMN and misoprostol significantly reduces the time to delivery; however, further well-designed studies with adequate sample sizes are needed to assess its safety and efficacy and determine its clinical role.
Keywords
Prolonged Pregnancy
Isosorbide Mononitrate
Misoprostol
Pregnancy
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Navid No
Volume 29, Issue 98
Summer 2026
Pages 48-61